Osteoporosis-Ca-vitD Flashcards
(3 cards)
Treatment of osteoporosis
Majority of OP medications are antiresorptive, aimed to slow bone turnover and increase BMD.
Antiresorptives
Bisphosphonates
Denosumab
Raloxifene
Oestrogen
Anabolic agents
These increase bone formation > resorption to reduce #s. The benefits of anabolic therapy are quickly lost after discontinuation, it is generally recommended to initiate antiresorptive therapy (bisphosphonate or alternative) to maintain bone density gains following a course of teriparatide.
PTH
- Teriparatide is a recombinant form of PTH (it contains 1-34 of its 84 amino acids), commonly used to treat OP in postmenopausal women, or men of high # risk. It acts similar to PTH to stimulate osteoblasts. Osteoblast formation is increased, and osteoblast apoptosis is inhibited, which results in an increase in bone turnover and formation. In addition, it causes a modest increase Ca2+ absorption from GIT and renal tubules. Efficacy has been demonstrated for 18-24months. Should not treat for >2yrs due to risk of bone resorption (must switch to antiresorptive therapy for maintenance). Contra-indicated in pts with Pagets. Montitor for hypercalcemia.
- PTH (containing 1-84 amino acids) is available for pts with chronic hypoparathyroidism despite Vit D / Ca supp’s
PTH receptor protein analogue
- Abaloparatide is a PTHrP analogue that selectively binds to the PTH type 1 receptor, favouring bone formation, has some renal Ca2+ absorption but no GIT abs. Has less adverse effects (hypercalcemia) than teriparatide
Patients with OP who have poor response to treatment with the above
- these patients will have continued bone loss.
- may be due to poor adherence to therapy (the most likely cause; esp w oral bisphosphonates), antiresorptive agent may be of poor choice (too weak), low calcium intake, vit D insufficiency, difference in bioavailability, malabsorption, or that treatment was commenced too late (bone is too severely disrupted), concurrent antiresorptive meds/corticosteroids/PPI (chronic PPI use may lead to increased fractures. Possible explanation - PPI lowers gastric acid levels leading to reduced calcium absorption, secondary hyperPTH, increased bone loss and #s)
- management: ensure adequate intake of calcium supp, check vit D levels, consider alternative treatment (stronger agent, injectable, anabolic agent if already on strong antiresorptive)
https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC2686338/
UpToDate
https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC3513863/
https: //www.ncbi.nlm.nih.gov/pmc/articles/PMC2974811/#R47
Bisphosphonates
Zoledronic acid (zolendronate / zometa)
indication:
- Hypercalcemia secondary to cancer
- osteoporosis
Contraindication
CrCl <30ml/min (oncology use); <35 (non-oncology use)
Pre-treatment:
- ensure Ca and vit D adequately replete (unless pt already hypercalcemic then no need to replace either).
- avoid in pregnancy, ensure on adequate birth control
- check renal f^n. (No hepatic adjustment necessary)
SE’s
- flu like syx (give paracetamol post to reduce this)
- lower limb oedema (<21%)
- fatigue (40%)
- GI: nausea/vom (~30-40%), diarrhoea (24%), constip (30%)
- bone pain (50%), anaemia (22-33%), neutropenia, progression of ca
dose: depends on indication
- 4mg IV once for hyperCa2+ of malignancy then re-assess after 1/52 for rpt dose
- every 3-4/52 for metastatic solid tumors / bony lesions in multiple myeloma / androgen-deprivation therapy in prostate cancer
- 3monthly for met breast ca / prostate ca / multiple myeloma
- 5mg IV yearly for fracture prevention
- post-renal transplant bone loss: 4mg IV at week 2, and month 3 post engraftment
Duration
For fracture prevention
- treat for 3years
- if ongoing fracture risk remains high, consider extending duration for up to 6yrs or switch to alternative therapy
- if ongoing fracture risk low after 3yrs (not fragility #s, BMD stable), then give drug holiday for up to 5yrs. Recommence if BMD declining / other risk factors dictate.
Parathyroid physiology
Anatomy
- 4 small glands, posterior thyroid, middle of anterior neck
Function
Ca2+ and Phos homeostasis:
Low serum Ca: (1) Parathyroid gland responds to low serum Ca2+ ; (2) secretes PTH; (3) PTH has many effects (refer below) that ultimately leads to increase in serum Ca2+; (4) serum Ca2+ corrects, leads to less secretion of PTH. Effects of PTH are as follows:
- renal effects: PTH facilitates synthesis of active Vit D (calcitriol) in PCT (by enhacing production of an enzyme required to catalyse this process) + directly increases Ca2+ reabsorption in DCT and collecting duct + decreases Phos reabsorption in PCT (less phos means less Ca-phos precipitates and more ionised Ca)
- bone: PTH directly stimulates osteoblasts to increase RANKL expression (permits differentiation into osteoclasts) + inhibits secretion of osteoprotegrein (permits formation of osteoclasts). Osteoclasts then degrade hydroxyapatite 5)
- Gut: Vit D acts to permit absorption of Ca2+ from small intestine
High serum Ca (negative feedback loop): (1) parathyroid senses high seurm Ca2+; (2) reduces PTH secretion
https://www.ncbi.nlm.nih.gov/books/NBK499940/
